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  • American Society of Hematology  (18)
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  • 1
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 36-36
    Abstract: Abstract 36 Background. Nephrotic syndrome (NS) is frequently accompanied by thromboembolic complications such as renal vein thrombosis, deep vein thrombosis and pulmonary embolism. However, the cause of the hypercoagulable state in NS patients is not understood. In contrast to quiescent cells, membrane-derived microparticles have exposed phosphatidylserine which may support procoagulant enzyme complexes in thrombosis. Objectives. The aim of this work was to measure the type and quantity of MPs that expose PS in NS patients, and to evaluate the associated procoagulant activity (PCA). Methods. The subjects with membranous nephropathy (MN) or minimal change nephrotic syndrome (MCNS) were compared to healthy controls. Flow cytometry and confocal microscopy was used to evaluate microparticles. PCA was determined by clotting time and purified coagulation complex assays. Results. We found that the number of lactadherin+ MPs was significantly higher in each NS group MCNS (3230 ± 536)/MN (4642 ± 697) than that in the controls (1748 ± 239), furthermore, MPs in MN patients are significantly higher than ones in MCNS (P 〈 0.05; Table 1), which mostly derived from RBC and platelet membranes. The percentage of lactadherin+ RBCs was also significantly increased in each NS group, MN (9.7 ± 3.2%)/MCNS (5.1 ± 2.4%) patients compared to the controls (0.5 ± 0.2%). In addition, the mean percentage of lactadherin+ RBCs in MN showed significantly higher than that in MCNS (P 〈 0.05). In both NS groups, the percentage of lactadherin+ platelets was significantly higher than that in healthy control subjects (4.1 ± 1.1%) (P 〈 0.05 for both). Furthermore, patients in MN (11.5 ± 3.1%) also had significantly increased lactadherin+ platelets than in MCNS (7.3 ± 2.3%) (P 〈 0.05). By confocal laser-scanning microscope, nearly no staining by Alexa Fluro 488-lactadherin could be detected on RBCs or platelets membranes in healthy subjects, whereas a light green fluorescence on RBC and platelet with lactadherin accompanying vesiculation were observed in NS patients. PCA of RBCs/platelets from healthy individuals and NS patients was assessed by recalcification time assays, intrinsic, extrinsic FXa and prothrombinase assays. MPs shedding and PS exposure of RBCs/platelets were highly procoagulant in NS patients and blockade of PS with lactadherin inhibited over 90% of PCA. However, an anti-TF antibody had no significant inhibition effect (Figure 1). Conclusions. This is the first study to show that loss of RBCs/platelets membrane phospholipid asymmetry with increased PS exposure and MPs release may contribute to the hypercoagulable state of NS patients. The extent of PS exposure on cells and MPs may be a marker of thromboembolic risk in these patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 2
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2480-2480
    Abstract: Background: SCT400 is a recombinant, human-mouse chimeric anti-CD20 IgG1 monoclonal antibody and has the same variable regions and antigen-binding site as rituximab. SCT400 has the heavy and κ light chain constant regions of human IgG1 allotype G1m (1,17), which is common in Asians. There is only one amino acid difference between SCT400 and rituximab (V219A in the CH1 domain of the heavy chain). The phase Ⅱ study showed that pharmacokinetics, pharmacodynamics and safety of SCT400 are equivalent to rituximab in patients with CD20-positive non-Hodgkin lymphoma. Objectives: This phase III study aimed to evaluate the safety and efficacy of SCT400 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) compared with rituximab plus CHOP in patients with treatment-naïve diffuse large B-cell lymphoma (DLBCL) (ClinicalTrials.gov, identifier: NCT02772822). Methods: In this multicenter, randomized, single-blind, parallel active-controlled, non-inferiority, phase III study, patients were enrolled from 37 centers in China. Eligible patients were aged 18~75 years with histologically confirmed CD20-positive, treatment-naïve DLBCL; international prognostic index (IPI) 0~2; an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0~2. Patients were randomly assigned in a 2:1 ratio to receive either SCT400 plus CHOP (S-CHOP) or rituximab plus CHOP (R-CHOP) every 21 days cycle treatment for six cycles. The primary endpoint was objective response rate (ORR) after six cycles of therapy, assessed by an independent review committee, with a non-inferiority margin of -12%. The secondary endpoints were complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between October 19, 2016 and July 13, 2018, 534 patients were screened and 364 eligible patients were randomized to either the S-CHOP group (n=243) or R-CHOP group (n=121). Patient demographics and disease characteristics at baseline were well balanced between the two treatment groups. In the per protocol set (PPS), the best ORRs within six cycles of treatment were 94.5% (95% confidence interval [CI], 90.8% to 97.0%) and 94.1% (95%CI, 88.2% to 97.6%) in the S-CHOP and R-CHOP groups respectively, with an intergroup difference of 0.4% (95%CI, -4.7% to 5.6%, P=0.6569) (Figure 1A). The 95%CI lay on the positive side of the prespecified non-inferiority margin of -12%, meeting the criterion for non-inferiority. The results of using the full analysis set (FAS) were consistent with the primary efficacy analysis in the PPS. No significant differences were observed in the secondary efficacy endpoints, in either the PPS or the FAS (Figure 1B and Figure 2). There were no significant differences were observed in ≥1 adverse event (AE, 97.9% vs. 99.2%), grade≥3 AE (85.2% vs. 86.0%), serious AE (35.4% vs. 38.8%), treatment discontinuation due to AE (7.8% vs.12.4%) between S-CHOP and R-CHOP groups, respectively (Table 1). AEs of special interest occurred in 63.8% of patients in the S-CHOP group and in 59.5% of patients in R-CHOP group, including infection (46.5% vs. 46.3%), infusion-related reaction (20.2% vs. 17.4%), cardiotoxicity (17.7% vs. 11.6%), hepatitis B virus reactivation (1.2% vs. 3.3%), ileus and enterobrosis (1.2% vs. 0.8%), tumor lysis syndrome (0.0% vs. 0.8%) (Table 1). A total of 51 deaths were reported in the S-CHOP group (n=35, 14.4%) and R-CHOP group (n=16, 13.2%), and 10 deaths were due to AE (S-CHOP group: n=7, 2.9%; R-CHOP group: n=3, 2.5%) (Table 1). After treatment, study-drug related anti-drug antibodies (ADAs) were detected in 11(10.9%) patients in S-CHOP group and in 8(16.0%) patients in R-CHOP group (Table 1). Conclusion: SCT400 plus CHOP showed non-inferiority of efficacy to rituximab plus CHOP in patients with treatment-naïve DLBCL. The safety and immunogenicity profiles of SCT400 were comparable with rituximab, with no new treatment-related AE occurred. SCT400 could be a therapeutic option for DLBCL. Funding source: This study was supported by the sponsor, Sinocelltech Ltd., and by grants from the China National Major Project for New Drug Innovation (No. 2018ZX09736002 and No. 2017ZX09304015). Conflicts of interest: Liangzhi Xie is an employee of Sinocelltech Ltd. and has ownership interests in the company. All other authors declare no conflicts of interest. Figure 1 Figure 1. Disclosures Hu: Astellas Pharma, Inc.: Research Funding. Xie: Sinocelltech Ltd.: Current Employment, Current equity holder in publicly-traded company.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 3
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 5048-5048
    Abstract: Abstract 5048 Introduction: Novel drugs, such as bortezomib, have significantly improved the response rates in multiple myeloma (MM), but little has been reported on bortezomib-based therapies in Chinese patients. Methods: In the initial eight 28-day cycles, newly diagnosed ymptomatic patients were treated with combination therapy including bortezomib plus dexamethasone (PD) and the triplet combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), thalidomide (PDT) between February 1, 2006 and May 31, 2012. Among the above regimens, bortezomib (1. 3 mg/m2) was given intravenously on days 1, 4, 8, 11, while dexamethasone (20 mg/m2/day) was given intravenously on days 1–2, 4–5, 8–9, 11–12, adriamycin (10 mg/m2) was given intravenously on days 1–4, cyclophosphamide (200 mg/m2) was given intravenously on days 1–4 and thalidomide (100 mg) was administered orally each day. Results: The overall response rate (¡Ý partial response, PR) of all the 151 eligible patients was 88. 7% (including 29. 8% very good partial response (VGPR) and 25. 8% complete response/near complete response (CR/nCR). The responses per IMWG criteria for patients are shown in Table 2. The median PFS was 20. 3 months (95% CI: 14. 8–25. 8 months) in the patients who received PDT, 24. 8 months (95% CI: 20. 0–30. 0 months) in the patients who received PCD, 22. 9 months (95% CI: 17. 6–28. 2 months) in patients who received PAD and 21. 8 months (95% CI: 15. 3–28. 3 months) in the patients who received PD with no significant differences between the groups. The median OS for PD arm was 42. 0(95% CI: 20. 1–63. 9 months) months while other arms were not reached, but the median OS for PDT, PCD and PAD was significant longer than PD (P=0. 042, 0. 039, 0. 010). PFS and OS for patients with favorable cytogenetics were significantly longer than those with unfavorable cytogenetics by FISH. The frequently observed hematologic toxicities (Grade 3/4) were: thrombocytopenia (17. 00%), neutropenia (15. 00%) and anemia (8. 61%). The most common non-hematologic toxicities included (all Grades) peripheral neuropathy(57. 61%), fatigue(27. 15%), infection(23. 84%), constipation(22. 52%), herpes zoster(17. 22%) and diarrhea(15. 23%). Conclusions: Our experience indicated that bortezomib-based regimens were active and well-tolerated for MM patients, and triplet combinations were superior to PD. Serious Adverse events were rare in the Chinese patients with MM who received bortezomib-based chemotherapy. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 4
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1159-1159
    Abstract: Abstract 1159 Poster Board I-181 Background In allogeneic SCT, genetic factors such as donor and recipient gene polymorphisms of pro- and anti-inflammatory cytokines have been associated with the incidence and severity of GVHD. However, the influence of such donor and recipient gene polymorphisms on other outcomes, such as early infection after SCT, has seldom been described. TNFαa, TNF receptorII (TNFRII), IL-10 and TGF gene contain multiple single nucleotide polymorphisms (SNPs) in the promoter and codon region. We thus studied the association of this panel of candidate gene polymorphisms with the incidence of the first episodes of early bacterial infections within 100 days after allo-HSCT. Methods A total of 138 unrelated donor/recipient pairs, who had undergone HLA-matched allo-HSCT from January 2001 to March 2009 at the First Affiliated Hospital of Zhejiang University School of Medicine, were tested for TNFαa(TNFαa-857 C 〉 T, TNFαa-863 C 〉 A, TNFαa-1031 T 〉 C), TNFRII (codon196 T 〉 G), IL-10 (IL10-1082 A 〉 G, IL10-819 T 〉 C, IL10-592 A 〉 C), TGF (TGF-509 T 〉 C, TGF+869 C 〉 T) polymorphism allele frequencies and genotype. SNPs were analysed by Multiplex SnaPshot. We considered the first episodes of early bacterial infections within 100 days after allo-HSCT have developed when sepsis, pneumonia, or septic shock was diagnosed according to previously published criteria. Results (1) 133 patients achieved complete donor chimerism in the peripheral blood and 5 patients had graft failure. All patients achieved an absolute neutrophil count (ANC) greater than 0.5×109/L at day 13 (7∼22) and platelet recovery at day 15 (7∼64). The cumulative incidence of at least one bacterial infection was 47.8% (pneumonia and intestinal infection are the most popular) within 100 days after allo-HSCT. There is no significant difference in the time to neutrophil recovery in patients who experienced early bacterial infections with those who did not (13.6 vs 12.8,P=0.115). (2) The TNFαa-857 C/C genotype and TNFRII 196 T/T genotype of the donor were significantly associated with a higher risk of early bacterial infection ( for TNFαa-857 C/C genotype: 53.3% vs 29.0%, P=0.024 ; TNFRII 196 T/T genotype: 53.5% vs 33.3%, P=0.038); (3) The TGF-509 T/T genotype of the donor was significantly associated with a higher risk of early bacterial infection (62.5% vs 41.8, P=0.038); (4) Transplantation from donors with IL10-819 C/C genotype or IL10-592 C/C genotype were significantly associated with a higher risk of early bacterial infection (for IL10-819 C/C genotype: 71.4.1% vs 45.3%, P=0.034; IL10-592 C/C genotype: 70.0.1% vs 45.8%, P=0.055); (5) The genotypes of TNFαa-863, TNFαa-1031, IL10-1082 and TGF+869 were not found to be associated with the risk of early bacterial infection. Conclusions Recent studies have shown that the generation potential of IL-10 is influenced by the polymorphism of the IL-10 gene. The IL10-819*C allele and IL10-592 *C allele are associated with higher secretion of IL-10 than IL10-819*T allele and IL10-592*A allele. In our data, a higher risk of early bacterial infection with IL10-819 C/C and IL10-592 C/C genotype was postulated to be associated with a higher IL-10 production, which suppressed reactive T-cell response. These results, which is the first report of TNFαa, TNFRII, IL-10and TGF polymorphic features of Chinese population with the risk of early bacterial infection after HLA-matched unrelated allo-HSCT, suggest an interaction of the donor TNFαa-857C/C, TNFRII 196 T/T, IL10-819 C/C, IL10-592 C/C and TGF-509 T/T genotypes on risk of early infection. These results are helpful for predict allo-HSCT outcome, identify more suitable donors and clarify therapy on an individual patient basis. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3257-3257
    Abstract: Abstract 3257 Poster Board III-1 We previously demonstrated that the cellular level of the fusion oncoprotein BCR-ABL in chronic myelogenous leukemia (CML) could be regulated by the proteolysis via ubiquitin-proteasome pathway and arsenic sulfide (As4S4) could enhance this process to exert therapeutic effects against CML. However, the exact biochemical mechanism and molecules involved, including the ubiquitin E3 ligases of BCR-ABL, their modification sites and the topologic type of ubiquitination remain uncovered. In this work, by using immunoprecipitation (IP) /2D-nano-HPLC/MALDI-TOF-TOF, we found a number of components in ubiquitination process, such as ubiquitin, E1, E2 and E3 ligases in the BCR-ABL protein complex. Particularly, several E3 ligases including the CBL family E3 ligase c-CBL were identified. The in vitro ubiquitination experiments indicated that c-CBL was one of the E3 ligases of BCR-ABL. Overexpression and knockdown experiments of the c-CBL gene revealed it participated in the process of endogeneous BCR-ABL ubiquitination and turnover. The enforced overexpression of c-CBL could enhance the degradation of BCR-ABL and apoptosis of CML cells whereas the down regulation of c-CBL generated opposite effects. Furthermore, we mapped a domain of c-CBL as the interface to form complex with BCR-ABL based on the protein structure prediction. Either the identification of BCR-ABL ubiquitination sites or the interaction experiment among the c-CBL and BCR-ABL are undergoing. Our data thus suggest that induction of c-CBL may be a new therapeutic approach for CML. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 6
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5075-5075
    Abstract: Abstract 5075 Multiple myeloma (MM) is a malignant disorder characterized by abnormal proliferation of monoclonal, immunoglobulin producing plasma cells in the bone marrow. Studies with large samples have shown that molecular cytogenetic changes play an important role in the prognosis of MM. Based upon these findings, we tested cytogenetic aberrations of 65 patients with MM by conventional cytogenetics analysis and FISH technique in this study. Retrospective study was done on these cases for clinical features. Methods: This is a retrospective analysis of 65 patients with MM diagnosed between June 2007 and May 2010 including 13 relapsed cases and 52 newly diagnosed patients. Patients received bortezomib-based combination chemotherapy including bortezomib plus dexamethasone (BD) and the triplet combinations (bortezomib, adriamycin, dexamethasone (BAD), bortezomib, cytoxan, dexamethasone (BCD) and bortezomib, melphalan, prednisone (BMP) or traditional chemotherapy including doxorubicin, vincristine plus dexamethasone (VAD), melphalan plus dexamethasone (MP), melphalan, dexamethasone plus thalidomide (MPT)). To further clarify the correlation between cytogenetic and clinical features on patients with multiple myeloma, we used conventional cytogenetics analysis with R-banding technique and interphase fluorescence in situ hybridization (FISH) to describe the molecular cytogenetic characterization of bone marrow nucleated cells from 65 patients. SPSS (version 18.0) software was used for data analysis, χ2 tests or Fisher's exact test was used for betweengroup comparison of the discrete variables and Log- Rank was used for survival analysis. p 〈 0.05 reflects the remarkable significance. Results: 16.9% of patients (11/65) showed abnormal cytogenetic aberrations including 90.9% (10/11) cases with ultra complex aberration and complex aberration via conventional cytogenetics. In addition, we were able to show aberrations in 49.2% (32/65) of patients by interphase FISH analysis. Abnormalities of 13q14, 1q21, 14q32 and 17p13 were detected in 27.7% (18/65), 13.8% (9/65), 16.9% (11/65), and 29.2% (19/65) by FISH, respectively. 1q21 amplification is strongly associated with 13q14 mutation (P=0.008), demonstrating significant correlation between two. Abnormality of 13q14 deletion or 1q21 amplification were associated with lower levels of albumin (P 〈 0.05). Patients with 13q14 deletion frequently had stage III disease by DS and ISS staging, and compared with patients not detected on FISH analysis, they tended to have elevated serum levels of β2-microglobulin at diagnosis (P 〈 0.05). 17p13 deletion coexistent with 13q14 deletion frequently correlate with elevated serum levels of β2-microglobulin and advanced clinical staging. The median progression-free survival (PFS) of patients with 17p13 deletion or 17p13/13q14 aberrations were both 11.0m, significantly lower than patients with no detected abnormality (median PFS 19.0m) (P 〈 0.05). The median overall survival (OS) of patients with FISH negtive results was 38.0m, significantly higher than those with 13q14, 14q32 or 1q21 abnormality and 17p13/13q14 or more than three abnormalities (P 〈 0.05). Conclusions: This study validates myeloma cells are prone to show complex aberration and FISH is superior in the detection of cytogenetic aberrations to conventional cytogenetics analysis for patients with multiple myeloma. 1q21 had significant correlation to 13q abnormality. 17p13 deletion coexist with 13q14 deletion and 14q32 rearrangeent were used to associate with poor prognosis. 17p13 deletion or 17p13/13q14 deletion was associated with poorer PFS while abnormality of 13q14, 1q21,14q32, 17p13/13q14 or more than 3 abnormalities were correlate with poorer OS. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 7
    Online Resource
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    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4635-4635
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4635-4635
    Abstract: Background Platelets not only play an important role in the initiation of hemostasis and thrombosis, but also participate in the immune and inflammatory response. Most studies focus on the platelets-bacteria interaction and demonstrate that bacteria are capable of binding to, aggregating and activating platelets. Human platelets are reported to express several groups of TLRs, which participate in the inflammation process and monitoring host infection. Recent data from our laboratory demonstrated that Group B streptococci (GBS) could induce platelet aggregation and up-regulate the expression of CD62P and further study showed that platelet TLR2 might involve in the activation. GBS, or streptococcus agalactiae, is one of the most common cause of life-threatening sepsis, pneumonia and meningitis in neonates, pregnant women, the elderly and immunocompromised adults. Therefore, illuminating the mechanisms of GBS-induced platelet activation is important for providing the basis for platelets in defense against infection and immunity. Since increasing reports have shown that the PI3-K/Akt signaling pathway regulates platelet activation and hemostasis, so it is possible to research the TLR2 related signaling pathway. Methods 1. Platelets were from healthy volunteers (all genders, 25-52 years old) who had not taken any anti-platelet drugs (like aspirins, clopidogrel and abciximab) during the previous 30 days. GBS 639 were isolated from patient's venous blood. 2. Platelet aggregation, the expression of platelet CD62P and PAC-1 were used as the indicator of platelet activation. GBS-induced platelet aggregation was assayed by light transmission; platelet TLR2, CD62P and PAC-1 expression were determined by flow cytometry; AKT and AKT phosphorylation expression were determined by RT-PCR or western blot assay. In some experiments, platelets were pre-incubated with PI3-K specific inhibitors LY294002 or anti-TLR2 monoclonal antibody. 3. Statistical analysis: Data are reported as the mean ± SD. Treatment groups were compared with the appropriate control (s), and statistical significance was examined using the two-tailed t-test. Differences were considered significant when P 〈 0.05. All values were analyzed using SPSS version 17.0 software. Results 1. Platelet activation and TLR2 protein expression: Platelet aggregation, surface expression of TLR2, CD62P and PAC-1 induced by GBS were increased significantly on the platelets upon activation with GBS 639. However incubated with anti-TLR2 monoclonal antibody, they all decreased. 2. PI3-K/Akt signaling pathway: Real-time PCR showed that the PI3-K and Akt mRNA expression levels were increased significantly in the platelets stimulated with GBS 639. Western blot results showed that of Akt phosphorylation triggered by GBS was occurred as early as 15 min and increased gradually to reach a peak at 2 h post-infection and no significant changes were observed in total Akt protein expression during the infection. However, the expression of p-Akt, platelet aggregation and surface expression of CD62P and PAC-1 induced by GBS were significantly inhibited in the presence of a PI3-K inhibitor LY294002. 3. The relationship between TLR2 and PI3-K/Akt signaling pathway in platelet activation: Platelet p-Akt expression levels induced by GBS were significantly decreased after the activity of platelet TLR2 was blocked by anti-TLR2 monoclonal antibody, and no significant changes in total Akt protein expression. Conclusions GBS induced platelet activation through the TLR2-PI3-K/Akt signaling pathway in human platelets. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 8
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 4-5
    Abstract: Introduction: Treatment options continued to evolve in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with many novel treatments available in recent years. The current study aimed to describe characteristics and treatment patterns of patients with R/R DLBCL who received ≥3 lines of therapy (LOT) using recent real-world data. Methods: This study used the PharMetrics Plus administrative claims database to identify adult patients who had ≥1 inpatient claim or ≥2 outpatient claims for DLBCL (ICD-10: C83.3) between 10/01/2015 and 09/30/2019. Patients were selected if they had ≥6-months of continuous eligibility before the first DLBCL diagnosis (index diagnosis). To capture newly diagnosed patients, the study excluded patients who had a claim for a possible DLBCL diagnosis and other hematologic malignancies (except hematologic conditions that may transform into DLBCL) before the index diagnosis and those who had stem cell transplantation (SCT) as the first treatment without prior chemotherapy (CT). An algorithm was developed to define LOT. In general, a new LOT was indicated by addition of a new drug or re-initiation of the previous LOT after a gap of ≥90 days. Pharmacologic therapies were categorized as CT or chemoimmunotherapy (CIT) or novel agent-based therapy (including brentuximab vedotin, ibrutinib, venetoclax, lenalidomide, obinutuzumab, nivolumab and pembrolizumab). SCT was counted as consolidation therapy instead of a separate line, while chimeric antigen receptor T cells (CAR-T) was counted as a separate line with preparation included (e.g., leukapheresis, bridging therapy, and lymphodepletion). Patients who received a third LOT (3L) comprised the study population, with the index date defined as the initiation date of 3L pharmacologic therapy or the infusion date of 3L SCT or CAR-T. 3L treatment distribution was described separately before and after the first CAR-T approval for DLBCL (10/18/2017). Treatment duration of 3L pharmacologic therapies was analyzed using Kaplan-Meier (KM) analysis. The proportion of patients initiating 4L during the observed follow-up period were described for all patients receiving a 3L. Due to the limited follow-up time and a high proportion of censoring, the current data was not mature to estimate rates of 4L initiation at different time points based on the KM analysis. All analyses were conducted for the overall study population and by treatment. Results: Among the 3,559 DLBCL patients receiving ≥1L treatment, 92.3% were treated with rituximab-containing regimens and 68.9% with R-CHOP or similar in 1L. There were 160 (4.5%) patients who received ≥3 LOT, with a mean age of 58.5 years and 64.4% male. Before CAR-T approval, 51 patients received 3L: 52.9% received CT/CIT, 33.3% received novel agent-based therapy, and 13.7% received SCT. After CAR-T approval, 109 patients received 3L: 45.9%, 30.3%, 7.3%, and 16.5% received CT/CIT, novel agent-based therapy, SCT and CAR-T, respectively. There were some differences in patient characteristics across treatment groups. Specifically, CAR-T patients had a relatively lower mean Charlson Comorbidity Index (CCI) score (2.9). The novel therapy group had a shorter median time from index diagnosis to index date (10.3 months). SCT patients were younger (mean 56.6 years) but with a relatively higher mean CCI score (4.2). The median follow-up time was 5.0 months and varied across treatments: from 3.9 months for CAR-T to 5.7 months for SCT. Among patients receiving pharmacologic treatments, the median treatment duration was 3.1 months and 2.8 months for the CT/CIT and novel agent-based therapy groups, respectively. During a median follow-up time of & lt;6 months, a total of 51 (31.9%) patients initiated 4L. The proportion was 27.8% in the CAR-T group, 28.6% in the CT/CIT group, 38.0% in the novel therapy group and 33.3% in the SCT group. Conclusions: In patients with R/R DLBCL receiving 3L treatment post CAR-T approval, about 76% were treated with CT/CIT or novel agent-based therapies, though most of the novel agents are not indicated for DLBCL. CAR-T and SCT were used in 17% and 7% of patients, respectively. Treatment duration of 3L CT/CIT or novel agent-based therapies was short. A relatively high proportion of patients moved to the next LOT during a short follow-up period. These findings highlight the unmet need for more effective treatments among R/R DLBCL patients in 3L and later lines. Disclosures Xie: Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Wu:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liao:ADCT: Current Employment, Current equity holder in publicly-traded company. Du:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Noman:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Liang:Analysis Group, Inc.: Other: Employee of Analysis Group, Inc., which has received consultancy fees from ADC Therapeutics, Inc.. Camardo:ADCT: Current Employment, Current equity holder in publicly-traded company. Chen:ADCT: Current Employment, Current equity holder in publicly-traded company.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 1990-1990
    Abstract: Bortezomib significantly improved response rates in the treatment of patients with multiple myeloma (MM). However, the process of selecting an optimal bortezomib based regimen as the initial therapy of MM remains ambiguous due to a lack of modern clinical trials demonstrating the efficacy of various bortezomib based treatments. Here, we report four bortezomib-based regimens for treatment of MM patients from three hematological treatment centers in China. Methods Newly diagnosed MM patients in three hematological centers in China between February 1, 2006 and May 31, 2013 were treated with combination therapies including bortezomib plus dexamethasone (PD), or triple combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), and thalidomide (PTD) every 28 days. Results The overall response rate (≥ partial response, ORR) of all the 215 eligible patients was 90.2%. The ORR for PCD, PAD, PTD and PD were 97.4%, 93.2%, 85.3% and 77.8% respectively, while the effects with VGPR or better were 63.7%, 62.7%, 44.2% and 37.8% respectively. The effect of ORR, VGPR and CR/nCR for PCD regimen was significantly better than PD scheme (P = 0.009, 0.011, 0.005 ). The median PFS of all the patients was 29.0 months with significant differences observed between groups (P =0.047). The median OS of all the patients was not reached, but triple combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), and thalidomide (PTD) were more efficient in treatment of MM patients compared to PD (P =0.005). The frequently observed toxicities were neutropenia, thrombocytopenia, fatigue, infection, herpes zoster, and peripheral neuropathy. Incidence of peripheral neuropathy (PN) in PTD group was significantly higher than other three groups, especially grade 2-3 PN. Treatment with anti-viral agent acyclovir significantly reduced the incidence of herpes zoster. Conclusions Our study demonstrated that bortezomib-based regimens were active and well-tolerated in the Chinese MM patients, and triple combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), and thalidomide (PTD) were more efficient for treatment of MM patient, and the patients received PCD or PAD demonstrated significant higher ORR compared to PD. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4444-4444
    Abstract: Purpose: Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is a rare and highly aggressive disease. The Ann Arbor staging system had been unsuitable to proper staging of ENKTL. This study was conducted to establish a new staging system specified for ENKTL, which can identify poor prognostic patients. Patients and Methods: Patients with untreated, centrally reviewed diagnosis of ENKTL were included in our study. The new staging system was established based on the study of single center consecutive patients treated with CHOP-like regimens with or without involved field radiotherapy (IFRT), then we initinated a multicenter confirmation study and conducted a multicenter prospective study to validate the new staging system. Results: From Jan 1997 to June 2006, 134 consecutive patients treated in the cancer center of Sun Yat-sen University were analyzed. The following was a summary of the classification system developed: stage I: lesions confined within nasal cavity or nasopharynx without local invasiveness (paranasal sinuses or bony or skin invasion); stage II: localized disease with local invasiveness; stage III: localized disease with regional lymph node involvement (cervical lymph nodes); and stage IV: disseminated disease (lymph nodes on both sides of diaphragm, multiple extranodal site). The distribution of stage I to IV using the new system and Ann Arbor system were 39.6%, 23.9%, 23.1%, 13.4% and 63.4%, 23.1%, 5.2%, 8.2%, respectively. The 5-year OS rate of stage I to IV using the new system were 29.5%, 23.4%, 21.3% and 0.07% compared with 23.8%, 21.3%, 0.0% and 0.0% using the Ann Arbor system. In the multicenter confirmation study conducted in 18 centers in China, 722 patients were analyzed. The results showed that the distribution of the new system compared with Ann Arbor system from stage I to IV were 24.1%, 34.9%, 18.3%, 22.7% vs 59.1%, 19.0%, 6.9%, 15.0%, respectively, and the 5-year OS rate of stage I to IV were 56.0%, 48.3%, 33.8%, 26.1% vs 50.7%, 39.1%, 10.8%, 28.0%, respectively. For the multicenter prospective study, 233 newly diagnosed ENKTL patients treated with non-CHOP-like regimens were enrolled and showed a balanced distribution of 17.2%, 39.9%, 19.3%, 23.6% vs 53.6%, 25.3%, 6.9%, 14.2% from stage I to IV and superior 5-year OS rate: 82%, 73%, 67%, 54% vs 75.2%, 65.6%, 46.9%, 73.8% from stage I to IV using the new system in compared with the Ann Arbor system. Conclusions: The new staging system with a more balanced distribution and a superior prognostic discrimination as compared with Ann Arbor staging system no matter for CHOP-like or non-CHOP-like regimens, is more suitable for ENKTL and can be recommended used in the future. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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